In the case of disease progression, patients initially assigned to the neratinib monotherapy arm will be given the option to add temsirolimus 8 mg IV once weekly.

All patients on combination therapy may be dose-escalated with respect to temsirolimus dose to 15 mg/week at the end of first cycle of treatment with the combination, if well tolerated and at the physician's discretion. In the event that the neratinib 240 mg/day plus temsirolimus 15 mg/week dose is not well tolerated, the patient will be subsequently dose reduced back to neratinib 240 mg/day plus temsirolimus 8 mg/week.

Dosing will be continuous on nominal 3-week cycles until evidence of progressive disease, unacceptable toxicity, or patient withdrawal of consent.

All eligible patients enrolled will have their disease measured radiographically at baseline. Patients will undergo radiographic evaluation of their disease every 6 weeks until disease progression or withdrawal from the study.